1. Field of the Invention
The invention relates to the field of vaccine compositions and more particularly to vaccine compositions comprising at least one antigen formed by the capsular polysaccharide of Haemophilus influenzae type b or high molecular weight polyribosylribitol phosphate coupled to tetanus anatoxin.
2. Description of the Related Art
An antigen which can be used for vaccine purposes in man in order to protect him from infections caused by Haemophilus influenzae type b is known in the prior art, and especially through the article "Quantitative and Qualitative Analyses of Serum Antibodies Elicited in Adults by Haemophilus influenzae Type b and Pneumococcus Type 6A Capsular Polysaccharide Tetanus Toxoid Conjugates" Rachel Schneerson et al, Infect. Immun. May 1986. This antigen is formed by a capsular polysaccharide of the bacteria, polyribosylribitol phosphate (or PRP), which is made T-dependent owing to coupling to a carrier protein, tetanus anatoxin. Trials carried out on rhesus children have shown, as this article reports, that the immune response was at one and the same time greater and earlier if the antigen was associated with aluminium hydroxide. However, as another article entitled "Clinical and Immunologic responses to the capsular polysaccharide of Haemophilus influenzae type b alone or conjugated to tetanus toxoid in 18-23 month-old children", Bo A. Claesson and al, The Journal of Pediatrics, May 1988, points out, it was noticed that this antigen, adsorbed on aluminium hydroxide, was less immunogenic after storage than the antigen kept in saline solution, which may be due to degradation of the polysaccharide.
In order to resolve this problem of stability of the PRP-T, it was proposed in the prior art to lyophilize it. This solution, even though it allows the antigen to retain its immunogenic character in the course of time, shows some disadvantages, however, especially at the manufacturing level; the lyophilization and the particular operations of conditioning which it requires complicates the production process, which increases the cost. In addition, at the time of administration, it is necessary to take up the lyophilizate again, which means that it is necessary to have in addition to the lyophilizate a liquid for taking up this lyophilizate; this operation represents a supplementary constraint for the practitioner and presents, like any manipulation, the risk of being carried out badly.
In addition, a certain number of liquid vaccine combinations possess antigens adsorbed on an aluminium-based adjuvant and it would be advantageous to be able, without loss of immunogenicity, to add the antigen formed by the PRP-T to them. In fact, the solution proposed in the prior art and consisting in a special syringe with two compartments (a first compartment containing the PRP-T in lyophilized form and a second compartment containing the other antigens in aqueous suspension) whose contents are mixed for use only at the time of administration is not satisfactory either at the level of the costs of production or at the level of the operations to be carried out by the practitioner.
It is thus desirable to be able to have a liquid vaccine composition comprising the antigen formed by the PRP-T having a very good immunogenic character retained in the course of time, and whose conditions of manufacture allow production at the lowest cost.